CN110066782B - 基本上无动物蛋白的重组体弗林蛋白酶及其生产方法 - Google Patents
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- 229940039716 prothrombin Drugs 0.000 description 1
- 235000015136 pumpkin Nutrition 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
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- 239000011535 reaction buffer Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
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- 230000000717 retained effect Effects 0.000 description 1
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- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 239000012898 sample dilution Substances 0.000 description 1
- 229910052706 scandium Inorganic materials 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
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- 238000003860 storage Methods 0.000 description 1
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- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 150000003681 vanadium Chemical class 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- RZLVQBNCHSJZPX-UHFFFAOYSA-L zinc sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O RZLVQBNCHSJZPX-UHFFFAOYSA-L 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- Engineering & Computer Science (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
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- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
成分 | JDE项目号 | 浓度[g/kg] | BAP | BAS | BCS |
DMEM/F12 | 0200437 | 11.745 | X | X | X |
L-谷氨酰胺 | 0200444 | 0.600 | X | X | X1 |
酚红钠盐 | 0200425 | 0.008 | X | X | X |
二盐酸腐胺 | 0200233 | 0.0036 | -- | -- | X |
硫酸铁(II)七水合物 | 0200231 | 0.0006 | -- | -- | X |
乙醇胺 | 0200426 | 0.00153 | X | X | -- |
Synperonic F68 | 0200172 | 0.250 | X | X | X2 |
大豆胨 | 0200171 | 2.50 | X | -- | -- |
碳酸氢钠 | 0301012 | 2.00 | X | X | X |
WFI(注射用水) | F124 | 加1kg | X | X | X |
成分 | 浓度[g/kg] |
DMEM/F12(1:1) | 11.76 |
L-谷氨酰胺 | 0.6 |
乙醇胺 | 0.00153 |
Synperonic | 0.25 |
腐胺·2HCl | 0.0036 |
FeSO4·7H2O | 0.0006 |
CuSO4·5H2O | 0.00000125 |
NaHCO3 | 2.0 |
氨基酸 | BACD_24_06_014_026 | FUR_06/10_M04_K06 | FUR_06/10_M04_K07 |
峰面积[%] | 相对峰面积[%] | 相对峰面积[%] | |
天冬氨酸 | 100.00 | 24.04 | 9.88 |
谷氨酸 | 100.00 | 57.78 | 24.89 |
丝氨酸 | 100.00 | 14.37 | 15.35 |
天冬酰胺H2O | 100.00 | 15.03 | 19.17 |
甘氨酸 | 100.00 | 103.55 | 90.58 |
谷氨酰胺 | 100.00 | 19.26 | 23.14 |
组氨酸 | 100.00 | 45.59 | 45.32 |
苏氨酸 | 100.00 | 63.09 | 61.39 |
精氨酸 | 100.00 | 72.22 | 74.25 |
丙氨酸 | 100.00 | 1513.36 | 1518.46 |
脯氨酸 | 100.00 | 58.54 | 55.36 |
酪氨酸 | 100.00 | 46.37 | 47.63 |
胱氨酸 | 100.00 | 53.43 | 56.39 |
缬氨酸 | 100.00 | 42.75 | 42.11 |
甲硫氨酸 | 100.00 | 13.23 | 11.51 |
异亮氨酸 | 100.00 | 48.39 | 48.79 |
亮氨酸 | 100.00 | 23.58 | 20.63 |
赖氨酸 | 100.00 | 41.85 | 40.65 |
苯丙氨酸 | 100.00 | 34.99 | 33.00 |
色氨酸%: | 100.00 | 69.1 | 68.8 |
实验 | glc | gln | pH | D | CC | μ | Furin | P | qP |
FUR_06/10-M04 | [g/L] | [g/L] | NOVA | [1/d] | [1E6/mL] | [1/d] | [IU/mL] | [kIU/L/d] | [IU/C/d]*106 |
天数6-9 | 1.58 | 0.10 | 7.16 | 0.494 | 2.35 | 0.548 | 306.55 | 151 | 64 |
实验 | glc | gln | pH | D | CC | μ | Furin | P | qP |
FUR_06/10-M04 | [g/L] | [g/L] | NOVA | [1/d] | [1E6/mL] | [1/d] | [IU/mL] | [kIU/L/d] | [IU/C/d]*106 |
天数15-21 | 1.47 | 0.35 | 7.16 | 0.668 | 2.27 | 0.673 | 352.68 | 236 | 104 |
实验 | glc | gln | pH | D | CC | μ | Furin | P | qP |
FUR_06/10-M04 | [g/L] | [g/L] | NOVA | [1/d] | [1E6/mL] | [1/d] | [IU/mL] | [kIU/L/d] | [IU/C/d]*106 |
天数26-29 | 1.37 | 0.38 | 7.13 | 0.713 | 2.20 | 0.695 | 373.80 | 267 | 121 |
氨基酸 | 峰面积[%] | 相对峰面积[%] | 相对峰面积[%] |
BACD-24-030-057 | FUR 06/17_F04-K07 | FUR 06/17_F04-K15 | |
甲硫氨酸 | 100.0 | 47.5 | 61.7 |
亮氨酸 | 100.0 | 50.3 | 65.4 |
苯丙氨酸 | 100.0 | 50.1 | 65.2 |
成分 | 基础培养基 | 优化培养基 |
浓度[g/kg] | 浓度[g/kg] | |
DMEM/F12(1:1) | 11.76 | 11.76 |
L-谷氨酰胺 | 0.6 | 0.9 |
D-葡萄糖 | -- | 1.5 |
乙醇胺 | 0.00153 | 0.00153 |
Synperonic | 0.25 | 0.25 |
腐胺·2HCl | 0.0036 | 0.0036 |
甲硫氨酸 | -- | 0.01 |
亮氨酸 | -- | 0.04 |
苯丙氨酸 | -- | 0.01 |
FeSO4·7H2O | 0.0006 | 0.0006 |
CuSO4·5H2O | 0.00000125 | 0.00000125 |
NaHCO3 | 2.0 | 1.5 |
发酵批号 | 温度[℃] | pH |
FUR_06/43-B07 | 35.1 | 7.20 |
FUR_06/43-B05 | 35.8 | 7.10 |
FUR_06/40-B03 | 35.8 | 7.30 |
FUR_06/40-B01 | 36.5 | 7.20 |
FUR_06/43-B02 | 36.5 | 7.20 |
FUR_06/40-B08 | 37.2 | 7.10 |
FUR_06/40-B04 | 37.2 | 7.30 |
FUR_06/40-B06 | 37.9 | 7.20 |
发酵批号 | 温度 | pH | CC | μ | Furin | P1) | qP1) | 存活率 |
[℃] | [106/mL] | [1/d] | [IU/mL] | [kIU/L/d] | [U/106/d] | [%] | ||
FUR_06/43-B07 | 35.1 | 7.20 | 1.74 | 0.595 | 930 | 543 | 312 | 97.7 |
FUR_06/40-B03 | 35.8 | 7.30 | 1.64 | 0.632 | 621 | 379 | 232 | 97.6 |
FUR_06/43-B05 | 35.8 | 7.10 | 1.73 | 0.647 | 683 | 429 | 250 | 98.5 |
FUR_06/40-B01 | 36.5 | 7.20 | 1.78 | 0.696 | 439 | 309 | 174 | 97.9 |
FUR_06/43-B02 | 36.5 | 7.20 | 1.66 | 0.684 | 454 | 310 | 186 | 96.8 |
FUR_06/40-B04 | 37.2 | 7.30 | 1.71 | 0.642 | 284 | 184 | 108 | 96.8 |
FUR_06/40-B08 | 37.2 | 7.10 | 1.68 | 0.652 | 338 | 215 | 128 | 98.3 |
FUR_06/40-B06 | 37.9 | 7.20 | 1.52 | 0.473 | 143 | 65 | 43 | 96.1 |
发酵批次 | 体积 | 模式 | D | μ | CC | 弗林蛋白酶 | P |
[1d] | [1d] | [1E6/mL] | [1U/mL] | [kIU/L/d] | |||
FUR_06_51-F04 | 10L | 恒化 | 0.494 | 0.497 | 1.67 | 401.4 | 198 |
FUR_06_50-F03 | 10L | 分批补料 | -- | 0.637 | 2.22(结束)1) | 539.8 | 2382) |
FUR_07/06-F071 | 搅拌速度 | CC1) | 分流比 | Furin | μ | P3) |
Intevall | [rpm] | [106/ml] | 1:x | [IU/ml] | [d-1] | [KU/L/d] |
批次K02-K04 | 120 | 1.95 | 3.89 | 1197.8 | 0.680 | 445 |
K10-K12 | 50 | 1.50 | 3.13 | 812.0 | 0.570 | 276 |
参数 | 设定值 |
过滤收获物的温度 | 10-15℃ |
过滤面积 | 14m2 |
进料压力 | 0.9-1.5bar |
滞留压力 | 0.7-1.2bar |
渗透压力 | 0-0.1bar |
跨膜压力 | 0.7-1.0bar |
比漫流流速(流送流速) | 300-600L/h/m2 |
比渗透流速 | 15-40L/h/m2 |
浓缩系数 | 20-30 |
加工时间 | 3-4h |
参数 | 设定值 |
过滤面积 | 14m2 |
进料压力 | 0.9-1.5bar |
滞留压力 | 0.7-1.2bar |
渗透压力 | 0-0.1bar |
跨膜压力 | 0.7-1.0bar |
比漫流流速(流送流速) | 300-600L/h/m2 |
比渗透流速 | 7-20L/h/m2 |
目标电导率 | <2mS/cm |
渗滤速度(V渗透液/V滞留液) | 4-5.5 |
加工时间 | 0.75-1.25h |
色谱分离步骤 | 缓冲液/产品 | 线性流速 | 数量 | |
cm/h | CV1) | |||
1 | 酸洗 | ES4在线稀释至0.2M醋酸 | 300 | 1 |
2 | 平衡 | EP2 | 150 | 37 |
3 | 吸附 | 35-45L渗滤产品 | 150 | |
4 | 平衡 | EP2 | 150 | 30 |
5 | 洗涤 | WPF | 150 | 10 |
6 | 梯度洗脱 | EL1/MMC洗脱物 | 150 | 15 |
7 | 洗脱II | EL2/MMC洗脱物 | 150 | 10 |
8 | 再生 | ES4 | 150 | 10 |
9 | 再生 | SHD | 150 | 10 |
方法 | 目的 | 评论 |
荧光底物切割 | 酶活性 | 低分子量底物 |
弗林蛋白酶应用实验 | 酶活性,熟化有效性 | rVWF底物 |
SDS-PAGE | 蛋白组合物 | 蛋白印迹实验 |
IEF | 蛋白组合物 | 考马斯染色,蛋白印迹实验 |
RP-HPLC | 蛋白组合物 | 蛋白指纹图谱 |
弗林蛋白酶批号恒化模式 | Furin活性 | 应用测试活性 | 成熟度 |
[U/ml] | [U/U] | [%] | |
ORFUCHR06002MMC01 | 28231 | 0.7 | >95 |
ORFUCHR06002MMC02 | 16307 | 0.4 | >95 |
ORFUCHR06002MMC03 | 44854 | 1.1 | >95 |
ORFUCHR06002MMC04 | 39102 | 1.3 | >95 |
ORFUCHR06002MMC05 | 71871 | 1.0 | >95 |
ORFUCHR06002MMC06 | 44292 | 1.0 | >95 |
ORFUCHR06002MMC07 | 68728 | 1.0 | >95 |
ORFUCHR06002MMC08 | 68510 | 1.0 | >95 |
平均值 | 47737 | 0.58 | >95 |
弗林蛋白酶批号重复分批补料 | Furin活性 | 应用测试活性 | 成熟度 |
[U/ml] | [U/U] | [%] | |
ORFUCHR07001MMC01 | 77090 | 0.5 | >95 |
ORFUCHR07001MMC02 | 68450 | 0.5 | >95 |
ORFUCHR07001MMC03 | 87420 | 0.5 | >95 |
平均值 | 77653 | 0.5 | >95 |
弗林蛋白酶批号重复分批补料 | Furin活性 | 应用测试活性 | 成熟度 |
[U/ml] | [U/U] | [%] | |
ORFUCHR07002MMC01 | 91200 | 0.5 | >95 |
ORFUCHR07002MMC02 | 96400 | 0.5 | >95 |
ORFUCHR07002MMC03 | 95020 | 0.5 | >95 |
ORFUCHR07002MMC04 | 85690 | 0.3 | >95 |
ORFUCHR07002MMC05 | 102670 | 0.6 | >95 |
ORFUCHR07002MMC06 | 88090 | 1.0 | >95 |
平均值 | 93178 | 0.6 | >95 |
实验 | MCB | WCB | MEPC |
生产率:弗林蛋白酶活性测试 | X | X | X |
测序 | X | --- | X |
定量PCR(基因拷贝数) | X | --- | X |
DNA印迹法 | X | --- | X |
蛋白印迹法 | X | --- | X |
实验 | MCB | WCB | MEPC |
同工酶分析 | X | X | X |
Claims (14)
Priority Applications (1)
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PCT/US2008/087732 WO2009088713A1 (en) | 2007-12-31 | 2008-12-19 | Substantially animal protein-free recombinant furin and methods for producing same |
CN2008801240838A CN101910401A (zh) | 2007-12-31 | 2008-12-19 | 基本上无动物蛋白的重组体弗林蛋白酶及其生产方法 |
CN201811405688.6A CN110066782B (zh) | 2007-12-31 | 2008-12-19 | 基本上无动物蛋白的重组体弗林蛋白酶及其生产方法 |
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ES2416079T3 (es) * | 2007-05-22 | 2013-07-30 | Baxter International Inc. | Proceso de purificación preparatoria de furina humana |
PL2240578T3 (pl) | 2007-12-31 | 2019-09-30 | Baxalta GmbH | Rekombinowana furyna zasadniczo wolna od białka zwierzęcego i sposoby jej wytwarzania |
US8241623B1 (en) | 2009-02-09 | 2012-08-14 | David Bermudes | Protease sensitivity expression system |
CN103097522A (zh) | 2010-07-08 | 2013-05-08 | 巴克斯特国际公司 | 在细胞培养物中生产重组adamts13的方法 |
US20140051832A1 (en) * | 2011-03-11 | 2014-02-20 | Universidade De São Paulo - Usp | Method for the production of recombinant human factor viii |
SG10201604488TA (en) * | 2011-06-02 | 2016-07-28 | Baxter Int | Formulations Of Recombinant Furin |
TWI666319B (zh) * | 2014-08-12 | 2019-07-21 | 美商巴克斯歐塔公司 | 在分泌furin之哺乳動物表現系統中生產經完全加工且具功能性之因子X |
SG11201705103WA (en) | 2014-12-22 | 2017-07-28 | Genzyme Corp | Methods of culturing a mammalian cell |
CA3068121A1 (en) | 2017-06-23 | 2018-12-27 | Baxalta Incorporated | Purification of factor viii subspecies |
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AT407750B (de) | 1999-02-19 | 2001-05-25 | Immuno Ag | Verfahren zur herstellung einer vwf-präparation |
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